Q1(d). LDA at -78°C: kinetic enolate of 2-phenylcyclohexanone

Introduction. 2-Phenylcyclohexanone has two sets of α-hydrogens: one tertiary, benzylic H on C-2 and two secondary H on C-6. LDA is a strong, bulky, non-nucleophilic base; at -78°C in THF deprotonation is fast and irreversible, so the enolate formed fastest (kinetic enolate) is the one obtained.

Scheme: LDA removes the more accessible C-6 hydrogen; the enolate carbon attacks MeI.

1. C. The C-2 hydrogen is more acidic (benzylic) but is tertiary and shielded by the phenyl ring. The bulky (iPr)₂N⁻ removes a less hindered C-6 hydrogen through a cyclic six-membered transition state with Li bound to the carbonyl oxygen. C = lithium 6-phenylcyclohex-1-en-1-olate (the less substituted enolate).
2. At -78°C with no excess ketone there is no proton exchange, so C does not equilibrate to the more stable, conjugated (thermodynamic) enolate C1=C2–Ph.
3. D. The enolate α-carbon (C-6) attacks CH₃I by SN2 (C-alkylation): D = 2-methyl-6-phenylcyclohexan-1-one (the new methyl and the phenyl on the two different α-carbons; a cis/trans mixture that favours the diequatorial isomer on equilibration).
4. Under thermodynamic conditions (NaH or Et₃N/Me₃SiCl with heating, or excess ketone) the conjugated enolate forms instead and methylation gives 2-methyl-2-phenylcyclohexanone.

Conclusion. C = kinetic lithium enolate formed by removal of the C-6 hydrogen; D = 2-methyl-6-phenylcyclohexan-1-one (major). The more substituted 2-methyl-2-phenyl ketone would need thermodynamic conditions.

Application. Kinetic (LDA, -78°C) versus thermodynamic enolate control decides the site of alkylation and aldol reactions in steroid and terpene syntheses.